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Molecular dynamics simulations of heterogeneous cell membranes in response to uniaxial membrane stretches at high loading rates

The chemobiomechanical signatures of diseased cells are often distinctively different from that of healthy cells. This mainly arises from cellular structural/compositional alterations induced by disease development or therapeutic molecules. Therapeutic shock waves have the potential to mechanically...

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Autores principales: Zhang, Lili, Zhang, Zesheng, Jasa, John, Li, Dongli, Cleveland, Robin O., Negahban, Mehrdad, Jérusalem, Antoine
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5559491/
https://www.ncbi.nlm.nih.gov/pubmed/28814791
http://dx.doi.org/10.1038/s41598-017-06827-3
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author Zhang, Lili
Zhang, Zesheng
Jasa, John
Li, Dongli
Cleveland, Robin O.
Negahban, Mehrdad
Jérusalem, Antoine
author_facet Zhang, Lili
Zhang, Zesheng
Jasa, John
Li, Dongli
Cleveland, Robin O.
Negahban, Mehrdad
Jérusalem, Antoine
author_sort Zhang, Lili
collection PubMed
description The chemobiomechanical signatures of diseased cells are often distinctively different from that of healthy cells. This mainly arises from cellular structural/compositional alterations induced by disease development or therapeutic molecules. Therapeutic shock waves have the potential to mechanically destroy diseased cells and/or increase cell membrane permeability for drug delivery. However, the biomolecular mechanisms by which shock waves interact with diseased and healthy cellular components remain largely unknown. By integrating atomistic simulations with a novel multiscale numerical framework, this work provides new biomolecular mechanistic perspectives through which many mechanosensitive cellular processes could be quantitatively characterised. Here we examine the biomechanical responses of the chosen representative membrane complexes under rapid mechanical loadings pertinent to therapeutic shock wave conditions. We find that their rupture characteristics do not exhibit significant sensitivity to the applied strain rates. Furthermore, we show that the embedded rigid inclusions markedly facilitate stretch-induced membrane disruptions while mechanically stiffening the associated complexes under the applied membrane stretches. Our results suggest that the presence of rigid molecules in cellular membranes could serve as “mechanical catalysts” to promote the mechanical destructions of the associated complexes, which, in concert with other biochemical/medical considerations, should provide beneficial information for future biomechanical-mediated therapeutics.
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spelling pubmed-55594912017-08-18 Molecular dynamics simulations of heterogeneous cell membranes in response to uniaxial membrane stretches at high loading rates Zhang, Lili Zhang, Zesheng Jasa, John Li, Dongli Cleveland, Robin O. Negahban, Mehrdad Jérusalem, Antoine Sci Rep Article The chemobiomechanical signatures of diseased cells are often distinctively different from that of healthy cells. This mainly arises from cellular structural/compositional alterations induced by disease development or therapeutic molecules. Therapeutic shock waves have the potential to mechanically destroy diseased cells and/or increase cell membrane permeability for drug delivery. However, the biomolecular mechanisms by which shock waves interact with diseased and healthy cellular components remain largely unknown. By integrating atomistic simulations with a novel multiscale numerical framework, this work provides new biomolecular mechanistic perspectives through which many mechanosensitive cellular processes could be quantitatively characterised. Here we examine the biomechanical responses of the chosen representative membrane complexes under rapid mechanical loadings pertinent to therapeutic shock wave conditions. We find that their rupture characteristics do not exhibit significant sensitivity to the applied strain rates. Furthermore, we show that the embedded rigid inclusions markedly facilitate stretch-induced membrane disruptions while mechanically stiffening the associated complexes under the applied membrane stretches. Our results suggest that the presence of rigid molecules in cellular membranes could serve as “mechanical catalysts” to promote the mechanical destructions of the associated complexes, which, in concert with other biochemical/medical considerations, should provide beneficial information for future biomechanical-mediated therapeutics. Nature Publishing Group UK 2017-08-16 /pmc/articles/PMC5559491/ /pubmed/28814791 http://dx.doi.org/10.1038/s41598-017-06827-3 Text en © The Author(s) 2017 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Zhang, Lili
Zhang, Zesheng
Jasa, John
Li, Dongli
Cleveland, Robin O.
Negahban, Mehrdad
Jérusalem, Antoine
Molecular dynamics simulations of heterogeneous cell membranes in response to uniaxial membrane stretches at high loading rates
title Molecular dynamics simulations of heterogeneous cell membranes in response to uniaxial membrane stretches at high loading rates
title_full Molecular dynamics simulations of heterogeneous cell membranes in response to uniaxial membrane stretches at high loading rates
title_fullStr Molecular dynamics simulations of heterogeneous cell membranes in response to uniaxial membrane stretches at high loading rates
title_full_unstemmed Molecular dynamics simulations of heterogeneous cell membranes in response to uniaxial membrane stretches at high loading rates
title_short Molecular dynamics simulations of heterogeneous cell membranes in response to uniaxial membrane stretches at high loading rates
title_sort molecular dynamics simulations of heterogeneous cell membranes in response to uniaxial membrane stretches at high loading rates
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5559491/
https://www.ncbi.nlm.nih.gov/pubmed/28814791
http://dx.doi.org/10.1038/s41598-017-06827-3
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